1. Field of the Invention
This invention relates to devices and methods for the noninvasive determination of in vivo concentrations of analytes or evaluation of a disease state, and more particularly, the noninvasive determination of in vivo concentrations of analytes or evaluation of a disease state wherein temperature is controlled and varied between preset boundaries.
2. Discussion of the Art
Non-invasive monitoring of concentrations of analytes in the human body by means of optical devices and optical methods is an important tool for clinical diagnosis. “Non-invasive” (alternatively referred to herein as “NI”) monitoring techniques measure in vivo concentrations of analytes in the blood or in the tissue without the need for obtaining a blood sample from the human body. As used herein, a “non-invasive” technique is one that can be used without removing a sample from, or without inserting any instrumentation into, the human body. The ability to determine the concentration of an analyte, or a disease state, in a human subject without performing an invasive procedure, such as removing a sample of blood or a biopsy specimen, has several advantages. These advantages include ease in performing the test, reduced pain and discomfort to the patient, and decreased exposure to potential biohazards. These advantages tend to promote increased frequency of testing, accurate monitoring and control of a disease condition, and improved patient care. Representative examples of non-invasive monitoring techniques include pulse oximetry for oxygen saturation (U.S. Pat. Nos. 3,638,640; 4,223,680; 5,007,423; 5,277,181; and 5,297,548). Another example of a non-invasive monitoring technique is the use of laser Doppler flowmetry for diagnosis of circulation disorders (J. E. Tooke et al., “Skin Microvascular Blood Flow Control in Long Duration Diabetics With and Without Complications”, Diabetes Research (1987) 5, 189–192). Other examples of NI techniques include determination of tissue oxygenation (WO 92/20273), determination of hemoglobin (U.S. Pat. No. 5,720,284), and determination of hematocrit (U.S. Pat. Nos. 5,553,615; 5,372,136; 5,499,627; and WO 93/13706). Determination of bilirubin was also described in the art (R. E. Schumacher, “Noninvasive Measurements of Bilirubin in the Newborn”, Clinics in Perinatology, Vol. 17, No. 2 (1990) 417–435, and U.S. Pat. No. 5,353,790).
Non-invasive diagnosis and monitoring of diabetes may be the most important non-invasive diagnostic procedure. Diabetes mellitus is a chronic disorder of carbohydrate, fat, and protein metabolism characterized by an absolute or relative insulin deficiency, hyperglycemia, and glycosuria. At least two major variants of the disease have been identified. “Type I” accounts for about 10% of diabetics and is characterized by a severe insulin deficiency resulting from a loss of insulin-secreting beta cells in the pancreas. The remainder of diabetic patients suffer from “Type II”, which is characterized by an impaired insulin response in the peripheral tissues (Robbins, S. L. et al., Pathologic Basis of Disease, 3rd Edition, W.B. Saunders Company, Philadelphia, 1984, p. 972). If uncontrolled, diabetes can result in a variety of adverse clinical manifestations, including retinopathy, atherosclerosis, microangiopathy, nephropathy, and neuropathy. In its advanced stages, diabetes can cause blindness, coma, and ultimately death.
Non-invasive determination of glucose has been the subject of several patents. U.S. Pat. Nos. 5,082,787; 5,009,230; 4,975,581; 5,379,764; 4,655,225; 5,551,422; 5,893,364; 5,497,769; 5,492,118; 5,209,231; and 5,348,003 describe a variety of optical methods for the noninvasive determination of glucose in the human body. However, all the previously mentioned patents are silent as to the effect of different layers of skin on optical measurements, or the effect of temperature on light penetration through these various layers of the skin. U.S. Pat. No. 5,935,062 recognizes the presence of skin layers and describes means to detect diffusely reflected light from the dermis and avoid light interacting with the epidermis by using a black barrier on the skin to separate specular reflectance and reflectance from the epidermis from reflected light that penetrated to the dermis. However, U.S. Pat. No. 5,935,062 is silent as to the effect of temperature on light penetrating through these layers of skin. The effect of temperature on the scattering and absorption properties of tissue has been of interest in the art. Thermal effects of laser excitation, photocoagulation, and temperature effect on skin optics have been described in the art. See, for example, W-C. Lin et al., “Dynamics of tissue reflectance and transmittance during laser irradiation”, SPIE Proceedings, 2134A Laser-Tissue Interaction V (1994) 296–303; and W—C. Lin, “Dynamics of tissue optics during laser heating of turbid media”, Applied Optics (1996) Vol. 35, No. 19, 3413–3420; J. Laufer et al., “Effect of temperature on the optical properties of ex vivo human dermis and subdermis”, Phys. Med. Biol. 43 (1998) 2479–2489; J. T. Bruulsema et al., “Optical Properties of Phantoms and Tissue Measured in vivo from 0.9–1.3 μm using Spatially Resolved Diffuse Reflectance”, SPIE Proceedings 2979 (1997) 325–334.
U.S. Pat. Nos. 3,628,525; 4,259,963; 4,432,365; 4,890,619; 4,926,867; 5,131,391; and European Patent Application EP 0472216 describe oximetry probes having heating elements designed to be placed against a body part. U.S. Pat. No. 5,148,082 describes a method for increasing the blood flow in a patient's tissue, during a photoplethsmography measurement, by heating the tissue with a semiconductor device mounted in a sensor. U.S. Pat. No. 5,551,422 describes a glucose sensor that is brought to a specified temperature, preferably somewhat above normal body temperature, with a thermostatically controlled heating system.
U.S. application Ser. No. 09/080,470, filed May 18, 1998, assigned to the assignee of this application, describes a non-invasive glucose sensor employing a temperature control. One purpose of controlling the temperature is to minimize the effect of physiological variables. U.S. application Ser. No. 09/098,049, filed Nov. 23, 1998, assigned to the assignee of this application, describes methods for determining optical properties of tissue having a plurality of layers. Both applications teach the use of temperature controlled optical element that is brought in contact with the skin.
Although a variety of detection techniques have been disclosed in the art, there is still no commercially available device that provides non-invasive glucose measurements with an accuracy that is comparable to the current commercially available invasive devices. Signals obtained by prior art methods reflect the analyte information of the tissue as if the tissue comprised a single uniform layer that has a single uniform temperature. As a result, current approaches to non-invasive metabolite testing, such as glucose monitoring, have not achieved acceptable precision and accuracy.
Thus, there is a continuing need for improved NI instruments and methods that are unaffected by variations in skin structures and layers or account for the effect of skin layers and the effect of temperature on the optical properties of these layers.